1. Field of the Invention
The present invention relates to an antimicrobial compound having improved resistance to conversion to a toxic compound or a dioxin-related compound.
2. Discussion of Related Art
Model et al., U.S. Pat. No. 3,800,048 and Model et al., U.S. Pat. No. 3,904,696 disclose halogenated hydroxydiphenyl ethers for controlling microorganisms. Of these, IRGASAN(copyright) DP 300 2,4,4xe2x80x2-dichloro-2xe2x80x2-hydroxydiphenyl ether produced by Ciba-Geigy Corporation, Ardsley, N.Y., is a well-known bacteriostat for industrial use. However at a temperature above about 200xc2x0 C., IRGASAN(copyright) DP 300 ether converts to a chlorinated dioxin, 2,8-dichlorodibenxo-p-dioxin (DCDD), which is structurally similar to compositions suspected of causing a variety of adverse health effects including cancer. 
Hence, in certain applications, it may be preferable to avoid use of IRGASAN(copyright) ether such as in plastic fabrications, which may involve high temperature. As such, there is a long-felt yet unsolved need for an antimicrobial compound that can be used in higher temperature fabrications without converting to a dioxin related compound.
Accordingly, a halogenated hydroxydiphenyl ether can be reacted with a compound that imparts a functional blocking moiety to prevent the conversion of the halogenated hydroxydiphenyl ether to dioxin related compounds at the higher temperatures typically used in plastic fabrication. In one embodiment, the compound comprises a blocked halogenated hydroxydiphenyl ether of the formula: 
where X1 is a halogen, X2 is chlorine or bromine, X3 is hydrogen, chlorine or bromine, X4 is chlorine, bromine, alkyl having 1 to 3 carbon atoms, xe2x80x94CHO, xe2x80x94CN or xe2x80x94NH2, X5 is chlorine, bromine, methyl, trichloromethyl, xe2x80x94CHO, xe2x80x94CN or xe2x80x94NH2, n is 1 or 2, and R is an ether linkage inhibiting group.
The invention also relates to a process for the preparation of a blocked halogenated hydroxydiphenyl ether comprising reacting a halogenated hydroxydiphenyl ether of the formula (II): 
with a blocking functionality providing compound.
In another embodiment, the invention relates to an antimicrobial composition comprising a plastic and a blocked halogenated hydroxydiphenyl ether of the formula (I) and to a process for the preparation of a plastic comprising incorporating an effective amount of an antimicrobial blocked halogenated hydroxydiphenyl ether of the formula (I) into the plastic.
In a preferred embodiment, an antimicrobial compound comprises a blocked halogenated hydroxydiphenyl ether of the formula: 
wherein X1 is a halogen, X2 is chlorine or bromine, X3 is hydrogen, chlorine or bromine, X4 is chlorine, bromine, alkyl having 1 to 3 carbon atoms, xe2x80x94CHO, xe2x80x94CN or xe2x80x94NH2, X5 is chlorine, bromine, methyl, trichloromethyl, xe2x80x94CHO, xe2x80x94CN or xe2x80x94NH2, n is 1 or 2, and R is an ether linkage inhibiting group such as trimethylsilyl, butyldimethylsilyl, tert-butyldimethylsilyl, trifluoroacetyl, pentafluoropropionyl and heptafluorobutyryl. Other examples of R include methoxy, methyl, amino and nitro groups that inhibit the formation of an ether linkage in reaction with X3.
A preferred compound of formula (I) is 2,4,4xe2x80x2-trichloro-2xe2x80x2-trimethylsilyloxy diphenyl ether according to the following formula (III): 
The compounds of formula (I) can be produced by reacting a halogenated hydroxydiphenyl ether of the formula: 
with a blocking functionality providing compound. In formula (II), X1 can be a halogen, X2 is chlorine or bromine, X3 is hydrogen, chlorine or bromine, X4 is chlorine, bromine, alkyl having 1 to 3 carbon atoms, xe2x80x94CHO, xe2x80x94CN or xe2x80x94NH2, X5 is chlorine, bromine, methyl, trichloromethyl, xe2x80x94CHO, xe2x80x94CN or xe2x80x94NH2, and n is 1 or 2.
The blocking functionality providing compound can be any compound that will react with the hydroxyl (xe2x80x94OH) of formula (II) to provide a functionality that will not react with X3 to result in an ether linkage between the 2,2xe2x80x2 positions. The reaction that provides the blocking functionality can be any suitable reaction, such as silylation, acylation, or alkylation.
Suitable blocking groups include silyl groups such as trimethylsilyl, butyldimethylsilyl and tert-butyldimethylsilyl. Preferred reagents for conducting the silylation reaction include bis(trimethylsilyl) trifluoroacetamide (BSTFA), N- or O-bis (trimethylsilyl) acetamide (BSA), hexamethyldisilazane (HDMS), N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA), N-methyl-N-(tert-butyldimethylsilyl)-trifluoroacetamide (MTBSTFA) and N-trimethylsilylimidazole.
The silyl reaction can be carried out in an organic solvent such as hexane, benzene, ether or the like in the absence of water. The reaction can be conducted at a suitable temperature, for example at a temperature between about 15xc2x0 and about 55xc2x0 C., preferably at room temperature. Generally, the reaction is completed within about 5 minutes to about 2 hours. Desirably, the reaction is completed within about 20 minutes and preferably within about 5 minutes. The concentration of silylation reagent to starting material can be in excess of 1.0:1.0 on a per mole basis, preferably in excess of 3.0:1.0.
Additionally, an acylation reaction can be used to provide a blocking functionality. The acylation can convert the 2xe2x80x2 hydroxyl group of the halogenated hydroxydiphenyl ether into an ester through the action of a carboxylic acid or carboxylic acid derivative. Preferred acylating agents include perfluoroacylimidazoles such as trifluoroacetylimidazole (TFAI), pentafluoropropionylimidazone (PFPI) and heptafluorobutyrylimidazole (HFBI).
The acylation reaction can be conducted in an organic solvent such as hexane or benzene at a temperature, for example, between about 15xc2x0 and about 55xc2x0 C., preferably at room temperature. Typically, the reaction is completed within 5 minutes but the reaction time can be extended to 1 hour. Concentration of acylation reagent to starting material can be in excess of 1.0:1.0 on a per mole basis, preferably in excess of 3.0:1.0.
Another suitable blocking providing reaction is alkylation wherein the hydrogen of the 2xe2x80x2 hydroxyl group of the halogenated hydroxydiphenyl ether is replaced with an aliphatic or aliphatic-aromatic group. Pentafluorobenzylbromide (PFBBr) is an example of a suitable alkylating compound.
The alkylation reaction can be carried out in a suitable organic solvent such as methylene chloride with tetrabutylammonium as a counter ion. The reaction can be conducted at a temperature for example between about 15xc2x0 and about 55xc2x0 C., preferably at room temperature. Typically, the reaction is completed within 5 minutes but the reaction time can be extended to 24 hours. Concentration of alkylating reagent to starting material can be in excess of 1.0:1.0 on a per mole basis, preferably in excess of 3.0:1.0.
The diphenyl ethers can be used in combination with other antimicrobially active substances. For example, the compound can be used with halogenated salicylic acid alkyl amides and anilides, with halogenated diphenyl ureas, with halogenated benzoxazoles or benzoxazolones, with polychlorohydroxydiphenyl methanes, with halogendihydroxydiphenyl sulfides, with bactericidal 2-imino-imidazolidines or tetrahydropyrimidines or with biocidal quaternary compounds or with certain dithiocarbamic acid derivatives such as tetramethyl thiuram disulphide. Various additional antimicrobial substances alone or in combination can be used with the diphenyl ethers to broaden the range of antimicrobial action and/or to provide a synergistic effect.
The diphenyl ether according to formula (I) can be incorporated into a plastic composition by addition into a polymer prior to the formation of pellets or by the addition of the ether in powder form immediately prior to or during a melt stage of a molding process. The diphenyl ether can be provided in a powder form, as pellets or as a blend of ether-containing pellets and non-ether-containing pellets.
The antimicrobial compound can be incorporated into a wide variety of plastics such as melt-extrudable thermoplastic polymers, which can be melt-processed to form non-woven webs or other shaped articles. The term xe2x80x9cplasticxe2x80x9d includes both thermosetting and thermoplastic materials. Particularly useful thermoplastic materials are thermoplastic polyolefins including any thermoplastic polyolefin used for the preparation of shaped articles by melt extrusion. Examples include polyethylene, polypropylene, poly(1-butene), poly(2-butene), poly(1-pentene), poly(2-pentene), poly(3-methyl-1-pentene), poly(4-methyl-1-1pentene), 1,2-poly-1,3-butadiene, 1,4-poly-1,3-butadiene, polyisoprene, polychloroprene, polyacrylonitrile, poly(vinyl acetate), poly-(vinylidene chloride), polystyrene and the like. Also included are blends of two or more polyolefins and copolymers.
The antimicrobial composition can be used with other suitable commercial plastic materials such as polyamide resins, acrylonitrile-butadiene-styrene (ABS) thermoplastic resins, polycarbonate resins, polycarbonate-ABS blends, PBT resins, acrylic-styrene-acrylonitrile (ASA), polyetherimides, interpolymers of PPO and expandable polystyrene EPS, polyphenylene ether+polystyrene (PPE-PPS blends), polyphenylene sulfide (PPS) based polymers, polybutylene terephthalate (PBT) based polymers, alloy blends of (PBT) and polycarbonate (PC), polypropylene, and polyethylene.
In this embodiment, the antimicrobial composition contains an effective amount of the antimicrobial compound. In this context, the term xe2x80x9ceffective amountxe2x80x9d is that amount which exhibits desirable antimicrobial activity at a point of use. In various alternative embodiments, the antimicrobial composition can contain between about 0.001 and about 5%, preferably between about 0.005 and about 3% and more preferably between about 0.01 and about 1% by weight of the antimicrobial compound.
The following example is provided in order that those skilled in the art will be better able to understand and practice the present invention. This example is intended to serve as an illustration and not as a limitation of the present invention as defined in the claims herein.